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A 59-year-old man was admitted to our hospital with hyponatremia. An endocrine examination indicated panhypopituitarism, and magnetic resonance imaging revealed a mass-like lesion in the pituitary gland. Sinus endoscopy revealed a fungal mass in the sphenoid sinus, and the patient was diagnosed with hypopituitarism due to aspergillosis of the central nervous system (CNS). The patient's hyponatremia resolved with hydrocortisone replacement. Although the right internal carotid artery was eventually occluded, antifungal medications were administered for the aspergillosis, and the patient's general condition improved. The patient's CNS lesions have remained under control since discharge. This is the first case to suggest that ACTH secretion may be relatively preserved in Aspergillus-induced hypopituitarism.

Objectives: To evaluate the efficacy and patient outcomes of pharmacist-physician collaborative protocol-based antimicrobial treatment regimens for antimicrobial stewardship., Methods: Patients treated for aspiration pneumonia due to stroke within 48 h after admission to Kochi Medical School Hospital (January 2019 to December 2022) were included. Primary outcomes were the cumulative number of days of antimicrobial treatment and length of hospital stay. Secondary outcomes included the percentage of patients under-dosed with first-choice antimicrobial agents and inpatient mortality., Results: Group A (66 patients) did not receive the antimicrobial treatment protocol, whereas group B (46 patients) did. There were no differences in the patient backgrounds. Group B had a significantly lower percentage of patients who were undertreated with the first-choice antimicrobial agent (9.1 % vs. 42.9 %). There was no significant difference in inpatient mortality between group A and group B (6.1 % vs. 4.3 %). The cumulative number of days of antimicrobial administration and the length of hospital stay were significantly lower in group B: 7.0 days (95 % CI, 6.0-8.0) vs. 9.0 days (95 % CI, 8.0-11.0) for antimicrobial administration, and 28.5 days (95 % CI, 22.0-35.0) vs. 43.0 days (95 % CI, 28.0-55.0) for hospital stay., Conclusions: Protocol-based antimicrobial treatment for aspiration pneumonia supports appropriate antimicrobial usage and improves patient quality of life. These findings will assist in the effective treatment of aspiration pneumonia in an aging society., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Aim: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus., Methods: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG-CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini-Mental State Examination and the Frontal Assessment Battery., Results: The TUG, TUG-CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre-CSF elimination results showed that the TUG-CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini-Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini-Mental State Examination results were significant predictors of the TUG-CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG-CV., Conclusions: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; 24: 693-699., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Campylobacter gracilis inhabits the gingival sulcus and has been reported to cause various periodontal diseases; it has rarely been reported to cause bacteremia. We describe a case of a two-year-old boy who presented with a consciousness disorder and was transferred to our hospital for treatment of a brain abscess. Magnetic resonance imaging (MRI) showed a 6-cm brain abscess in the right frontal lobe. Urgent drainage and antibiotic administration resulted in a favorable clinical course, and the patient was discharged on the 34th day of hospitalization. Streptococcus anginosus and C. gracilis were identified in the pus. Brain abscesses caused by C. gracilis have rarely been reported, which makes this a valuable case., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by the Kochi Organization for Medical Reformation and Renewal (to YA). . Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Arakawa et al.)

NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication., (© 2024. The Author(s).)

Objective: Cerebrospinal fluid (CSF) hypovolemia presents with orthostatic headaches due to CSF leakage. However, a direct association between the lack of CSF and clinical symptoms has not been found. CSF hypovolemia can be improved by refilling CSF. Therefore, we assessed the validity of a CSF refill test., Methods: From November 2019 to August 2021, we included 10 patients (≥18 years old) with potential CSF hypovolemia, clear orthostatic headaches, and a CSF opening pressure <10 cmH₂O. In the CSF refill test, 10 mL of artificial CSF was injected intrathecally. The primary outcome was improvement in orthostatic headache assessed using a visual analog scale (VAS), while the secondary outcomes were the 10-m walk time and adverse events. When the symptoms temporarily improved after intrathecal injection, the patients underwent radiologic imaging to identify the CSF leak, and an epidural blood patch was proposed accordingly., Results: All patients showed post-test improvements in the VAS score (median [interquartile range], pretest 63.0 [50.3-74.3] vs. post-test 1.5 [0.0-26.0]). The 10-m walk time also significantly improved (9.5 [8.5-10.2] s vs. 8.2 [7.9-8.7] s). One patient experienced temporary right leg numbness associated with a lumbar puncture. After radiologic investigation, 9 patients underwent epidural blood patches, of which 6 were completely cured, and 3 revealed partial improvement., Conclusions: The cerebrospinal fluid (CSF) refill test was safe and effective in demonstrating the direct association between the lack of CSF and clinical symptoms and may help predict the outcome of an epidural blood patch., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Acute embolic occlusion of the common carotid artery (CCA) alone is rare. However, once it occurs, recanalization is challenging due to the large volume of the clot, larger diameter of the CCA, and risk of procedure-related distal embolism into the intracranial arteries., Observations: The authors report two cases of acute embolic occlusion of CCA alone, caused by a cardiac embolus trapped at the proximal end of a preexisting atherosclerotic plaque at the cervical carotid bifurcation. In both cases, the CCA was successfully recanalized using retrograde thrombectomy in a hybrid operating room. In case 1, a 78-year-old male with acute right CCA occlusion underwent retrograde thrombectomy, where the cervical carotid bifurcation was exposed and incised, and the entire embolus was retrieved with forceps. Despite successful revascularization, massive bleeding from the CCA just after the retrieval remained a concern. In case 2, a 79-year-old female with acute right CCA occlusion underwent retrograde thrombectomy in the same manner. Because manual retrieval failed, a Fogarty balloon catheter inserted from the arteriotomy successfully retrieved the entire thrombus with minimal blood loss., Lessons: Retrograde thrombectomy through the arteriotomy of the cervical carotid bifurcation safely and effectively recanalizes acute embolic occlusion of the CCA alone.

Background and Objectives: The differences in clinical outcomes between endovascular coiling (EC) and surgical clipping (SC) in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) are controversial. Therefore, this study aimed to evaluate whether EC is superior to SC and identify risk factors in patients with poor-grade aSAH., Methods: We used data from the "Predict for Outcome Study of aneurysmal SubArachnoid Hemorrhage." World Federation of Neurological Societies (WFNS) grade III-V aSAH was defined as poor-grade aSAH, and unfavorable clinical outcomes (modified Rankin Scale scores 3-6) were compared between SC and EC after propensity score matching (PSM). In-hospital mortality was similarly evaluated. Predictors of unfavorable clinical outcomes were identified using multivariable analysis., Results: Ultimately, 1326 (SC: 847, EC: 479) and 632 (SC: 316, EC: 316) patients with poor-grade aSAH were included before and after PSM, respectively. Unfavorable clinical outcomes at discharge were significantly different between SC and EC before (72.0% vs 66.2%, P = .026) and after PSM (70.6% vs 63.3%, P = .025). In-hospital mortality was significantly different between groups before PSM (10.5% vs 16.1%, P = .003) but not after PSM (10.4% vs 12.7%, P = .384). Predictors of unfavorable clinical outcomes in both SC and EC were WFNS grade V, older than 70 years, and Fisher computed tomography (CT) grade 4. Predictors of unfavorable clinical outcomes only in SC were WFNS grade IV (odds ratio: 2.46, 95% CI: 1.22-4.97, P = .012) and Fisher CT grade 3 (4.90, 1.42-16.9, P = .012). Predictors of unfavorable clinical outcome only in EC were ages of 50s (3.35, 1.37-8.20, P = .008) and 60s (3.28, 1.43-7.52, P = .005)., Conclusion: EC resulted in significantly more favorable clinical outcomes than SC in patients with poor-grade aSAH, without clear differences in in-hospital mortality. The benefit of EC over SC might be particularly remarkable in patients with WFNS grade IV and Fisher CT grade 3., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Although non-stroke vertebral artery dissection (VAD) is diagnosed using MRI, detecting the subtle intravascular structure remains challenging. This study aimed to evaluate the validity of quantitative intravascular scanning based on novel zoomed high-resolution black blood (Z-HB) MRI for distinguishing VAD from other vessel pathologies., Methods: Twenty-one patients with non-stroke VAD and 18 with symptomatic atherosclerotic plaques in their vertebral artery underwent Z-HB MRI and subsequent profile curve processing. Axial Z-HB imaging was obtained from dissected and normal segments in patients with VAD and atherosclerotic plaque in patients with ischemia. We investigated the qualitative categorization of the scanning patterns of the intravascular signals. We also evaluated the quantitative ability of each profile curve to discriminate multiple vessel pathologies by analyzing the receiver operating characteristics curves., Results: Profile curve processing of 140 Z-HB images categorized the intravascular signal patterns into luminal, asymmetrical, and omega types. The asymmetrical type included both dissecting and atherosclerotic vessels, and the omega type included dissecting and normal vessels. In the asymmetrical type, quantitative evaluation successfully distinguished intramural hematomas of VAD from atherosclerotic plaque with an area under the curve of 0.80. The intimal flap of the VAD was distinguished from the blood flow artifact of the normal vessel with an area under the curve of 0.93 in the omega type., Conclusions: A combination of novel Z-HB MRI and profile curve processing provided an ultra-high-resolution analysis of the intravascular structure of non-stroke VAD and successfully distinguished VAD from normal vessels or atherosclerotic plaques., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To examine whether the Areal Deprivation Index (ADI), an indicator of the socioeconomic status of the community the patient resides in, is associated with delayed arrival at the hospital and poor outcomes in patients with acute ischaemic stroke from a prefecture-wide stroke database in Japan., Design: Retrospective study., Setting: Twenty-nine acute stroke hospitals in Kochi prefecture, Japan., Participants: Nine thousand and six hundred fifty-one patients with acute ischaemic stroke who were urgently hospitalised, identified using the Kochi Acute Stroke Survey of Onset registry. Capital and non-capital areas were analysed separately., Primary and Secondary Outcome Measures: Prehospital delay defined as hospital arrival ≥4-hour after stroke onset, poor hospital outcomes (in-hospital mortality and discharge to a nursing facility) and the opportunities of intravenous recombinant tissue plasminogen activator (rt-PA) and endovascular reperfusion therapy., Results: In the overall cohort, prehospital delay was observed in 6373 (66%) patients. Among individuals residing in non-capital areas, those living in municipalities with higher ADI (more deprived) carried a significantly higher risk of prehospital delay (per one-point increase, OR (95% CI) 1.45 (1.26 to 1.66)) by multivariable logistic regression analysis. In-hospital mortality (1.45 (1.02 to 2.06)), discharge to a nursing facility (1.31 (1.03 to 1.66)), and delayed candidate arrival ≥2-hour of intravenous rt-PA (2.04 (1.30 to 3.26)) and endovascular reperfusion therapy (2.27 (1.06 to 5.00)), were more likely to be observed in the deprived areas with higher ADI. In the capital areas, postal-code-ADI was not associated with prehospital delay (0.97 (0.66 to 1.41))., Conclusions: Living in socioeconomically disadvantaged municipalities was associated with prehospital delays of acute ischaemic stroke in non-capital areas in Kochi prefecture, Japan. Poorer outcomes of those patients may be caused by delayed treatment of intravenous rt-PA and endovascular reperfusion therapy. Further studies are necessary to determine social risk factors in the capital areas., Trial Registration Number: This article is linked to a clinical trial to UMIN000050189, No.: R000057166 and relates to its Result stage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this section, new arsenals for neurological treatment based on an open source are introduced. "Delytact" and "Stemirac" are discussed in this section. These two new arsenals have been accepted as cell and gene therapy products by the Ministry of Health, Labor, and Welfare. "Delytact" is a viral-gene therapy that targets malignant brain tumors, such as malignant gliomas, while "Stemirac" targets against spinal contusion via self-mesenchymal implantation. Both are permitted clinical arsenals in Japan.

Objective: Some aneurysmal subarachnoid hemorrhage (SAH) patients are delayed in their presentation. This can cause a washout of the subarachnoid hematoma and a potential misdiagnosis. As a result, they may suffer rerupture of the aneurysm and preventable deterioration. We investigated the factors that influence delayed SAH presentation., Methods: Aneurysmal SAH patients treated at 9 stroke centers from 2002 to 2020 were included. Age, gender, pre-SAH modified Rankin scale, World Federation of Neurological Surgeons grade, Fisher group, day of presentation, aneurysm treatment method, past history of cerebral stroke, comorbidity of hypertension and/or diabetes mellitus, and modified Rankin scaleat discharge were assessed retrospectively. We formed 2 groups based on the day of presentation after the onset of SAH: day 0-3 (early) and other (delayed). Logistic regression analyses detected the factors that influenced the day of presentation and outcome for SAH. A P- value <0.05 was considered significant., Results: Delayed presentation comprised 282 cases (6.3%) of 4507 included cases. Logistic regression analyses showed that patients in an urban area, of male gender, low WFNS grade and low Fisher group correlated significantly with a delayed presentation. But delayed presentation did not influence outcome at discharge., Conclusions: Area of residency and gender correlated with delayed presentation after SAH in Japan. Urbanization, male gender, and mild SAH lead patients to delay presentation. The factors underlying these tendencies will be analyzed in a future prospective study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Apathy is frequently observed in idiopathic normal pressure hydrocephalus (iNPH) and worsens cognitive impairment and gait disturbance. In this study, we evaluated the regions associated with apathy in iNPH using statistical imaging analysis on the whole brain, both in terms of cerebral blood flow and gray matter volume. Twenty-seven patients with iNPH were assigned to two groups based on their scores on the neuropsychiatric inventory items related to apathy; 18 patients were assigned to the group with apathy (iNPH + APA) and 9 to the group without apathy (iNPH - APA). The magnetic resonance images and cerebral blood flow single-photon emission computed tomography data of the two groups were compared using statistical parametric mapping 12. The regional gray matter volume of the right precuneus was significantly larger in the iNPH + APA group than in the iNPH - APA group, but the regional cerebral blood flow in any region of the brain was not significantly different between the two groups. These results suggested that the larger gray matter volume, which is thought to reflect gray matter compression, in the precuneus might be involved in apathy in iNPH., (© 2022. The Author(s).)

The "Izumo Study" revealed the incidence rate of subarachnoid hemorrhage (SAH) in Izumo City, Shimane Prefecture, Japan, from 1980 to 1998. However, no study has been published regarding the incidence of SAH in Shimane Prefecture after 1998. Most studies reporting the incidence of SAH in Japan have been conducted before 2000, although a few have been reported after 2000. This study aimed to assess the estimated age-adjusted incidence rate (AAIR) of SAH in Shimane Prefecture after 1998, following the Izumo Study. A retrospective study was conducted to identify the estimated AAIR of SAH in Shimane Prefecture, using the age-adjusted SAH mortality rate for this population from 1999 to 2017 and assuming that the case-fatality rate of SAH decreased by 0.7% annually from 45% in 1999 to 32.4% in 2017. We used linear regression analysis for trend to the estimated AAIR of SAH. Sensitivity analyses were also conducted by various case-fatality rates of SAH using assuming case-fatality rate based on previous reports. The estimated AAIR of SAH in Shimane Prefecture declined from 33.6 (95% confidence interval [CI]: 29.7-37.9) per 100,000 person-years in 1999, by 26.5%, to 24.7 (95% CI: 21.4-28.5) in 2017 (p < 0.01, r = 0.58). Declining trend of incidence rate of SAH in Shimane Prefecture from 1999 to 2017 was confirmed in this study.

Background: Use of 5-aminolevulinic acid for photodynamic malignant tumor diagnosis reportedly causes intraoperative hypotension (systolic blood pressure < 70 mmHg) during urologic surgery. However, its association with intraoperative hypotension in malignant glioma surgery and underlying mechanisms has not yet been elucidated.. This study aimed to investigate whether 5-aminolevulinic acid administration is associated with intraoperative hypotension in malignant glioma surgery and explore the mechanisms of 5-aminolevulinic acid-induced hypotension in vitro., Methods: In this retrospective multicenter cohort study, we investigated intracellular nitric oxide as a candidate mediator of hypotension in response to 5-aminolevulinic acid in vitro in human umbilical vein endothelial cell cultures., Results: Of 142 patients, 94 underwent 5-aminolevulinic acid-guided surgery. Systolic blood pressure was significantly lower throughout surgery with 5-aminolevulinic acid administration. 5-Aminolevulinic acid administration was an independent risk factor for intraoperative hypotension according to multivariable logistic regression analysis (89% vs. 56%; odds ratio = 6.72, 95% confidence interval [2.05-22.1], P = 002). In subgroup analysis of the 5-aminolevulinic acid group, increasing age and use of renin-angiotensin system inhibitors had a synergistic effect with 5-aminolevulinic acid on decreased blood pressure. In the vascular endothelial cell culture study, 5-aminolevulinic acid induced a significant increase in intracellular nitric oxide generation., Conclusions: 5-Aminolevulinic acid administration was associated with intraoperative hypotension in malignant glioma surgery, with increasing age and use of renin-angiotensin system inhibitors boosting the blood pressure-lowering effect of 5-aminolevulinic acid. According to in vitro results, the low blood pressure induced by 5-aminolevulinic acid may be mediated by a nitric oxide increase in vascular endothelial cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Stroke is a major cause of long-term disability, and there are few effective treatments that improve function in patients during the chronic phase of stroke. Previous research has shown that single systemic infusion of mesenchymal stem cells (MSCs) improves motor function in acute and chronic cerebral ischemia models in rats. A possible mechanism that could explain such an event includes the enhanced neural connections between cerebral hemispheres that contribute to therapeutic effects. In the present study, repeated infusions (3 times at weekly intervals) of MSCs were administered in a rat model of chronic stroke to determine if multiple dosing facilitated plasticity in neural connections., Methods: The authors induced middle cerebral artery occlusion (MCAO) in rats and, 8 weeks thereafter, used them as a chronic stroke model. The rats with MCAO were randomized and intravenously infused with vehicle only (vehicle group); with MSCs at week 8 (single administration: MSC-1 group); or with MSCs at weeks 8, 9, and 10 (3 times, repeated administration: MSC-3 group) via femoral veins. Ischemic lesion volume and behavioral performance were examined. Fifteen weeks after induction of MCAO, the thickness of the corpus callosum (CC) was determined using Nissl staining. Immunohistochemical analysis of the CC was performed using anti-neurofilament antibody. Interhemispheric connections through the CC were assessed ex vivo by diffusion tensor imaging., Results: Motor recovery was better in the MSC-3 group than in the MSC-1 group. In each group, there was no change in the ischemic volume before and after infusion. However, both thickness and optical density of neurofilament staining in the CC were greater in the MSC-3 group, followed by the MSC-1 group, and then the vehicle group. The increased thickness and optical density of neurofilament in the CC correlated with motor function at 15 weeks following induction of MCAO. Preserved neural tracts that ran through interhemispheric connections via the CC were also more extensive in the MSC-3 group, followed by the MSC-1 group and then the vehicle group, as observed ex vivo using diffusion tensor imaging., Conclusions: These results indicate that repeated systemic administration of MSCs over 3 weeks resulted in greater functional improvement as compared to single administration and/or vehicle infusion. In addition, administration of MSCs is associated with promotion of interhemispheric connectivity through the CC in the chronic phase of cerebral infarction.

Background: Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery., Methods: A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92)., Results: In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19-38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings., Conclusion: Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Delirium in patients with acute decompensated heart failure (ADHF) is associated with poor clinical outcomes. Although some medications have been reported as risk factors for delirium, their impact on patients with ADHF is still unclear. This study aimed to determine the association of specific medication use with delirium and their additive predictive value in models based on conventional risk factors., Methods and Results: In this single-center, retrospective study, 650 patients treated for ADHF were included. Fifty-nine patients (9.1%) had delirium. In multivariate analysis, anxiolytic benzodiazepines [odds ratio (OR): 6.4, 95% confidence interval (CI): 2.8-15], mechanical ventilation or noninvasive positive pressure ventilation (OR: 6.0, 95% CI: 2.9-12), depression (OR: 3.2, 95% CI: 1.5-6.5), intensive care or high care unit admission (OR: 2.9, 95% CI: 1.5-5.6), male sex (OR: 2.0, 95% CI: 1-3.7), and age (OR: 1.1, 95% CI: 1-1.1) were independently associated with severe delirium. The predictive model that included anxiolytic benzodiazepines had a significantly better discriminatory ability for the incidence of severe delirium than the conventional model., Conclusions: The use of anxiolytic benzodiazepines was independently correlated with severe delirium, and their use in models based on conventional risk factors had an additive value for predicting delirium in patients with ADHF., Competing Interests: The authors have declared that no competing interests exist.

Accumulating evidence indicates time-of-day variations in ischemic neuronal injury. Under ischemic conditions, Zn 2+ is massively released from hippocampal glutamatergic neurons, and intracellular Zn 2+ accumulation results in neuron death. Notably, excitatory amino acid carrier 1 (EAAC1), known as a cysteine transporter, is involved in Zn 2+ homeostasis, and its expressions exhibit a diurnal fluctuation. This study aimed to investigate whether time of day of an ischemic insult affects Zn 2+ accumulation and neuronal injury and determine whether altered Zn 2+ accumulation is modulated by EAAC1 diurnal fluctuation in the hippocampus in a mouse model of ischemic stroke. Mice subjected to transient global ischemia for 40 min at Zeitgeber time 18 (ZT18) (23:00) exhibited reduced Zn 2+ accumulation and neuronal death in the hilar region of the hippocampus compared to those at ZT4 (09:00). The EAAC1 protein expression in the hippocampus was increased at ZT18 relative to ZT4. Intracerebroventricular injection of a non-selective excitatory amino acid transporter inhibitor, DL-threo-β-benzyloxyaspartate, or a selective EAAC1 inhibitor, L-aspartic acid β-hydroxamate, increased ischemia-induced Zn 2+ accumulation and neuronal death in the hilus at ZT18. These findings suggest that ischemia-induced Zn 2+ accumulation displays circadian fluctuations through diurnal variations in EAAC1 expressions and affects susceptibility to ischemic neuronal injury in the hippocampal hilar region., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cerebrospinal fluid (CSF) hypovolemia is usually treated via an epidural blood patch (EBP). Accurate placement of the EBP at the site of CSF leakage is required for successful treatment of CSF hypovolemia. The thoracolumbar spine is evidently a common site of leakage, but because rates of detection of the leakage site via conventional imaging have historically not been high, there may be other common leakage sites. In this study, CSF leakage sites were identified via a combination of conventional imaging, a new method called the overflow leak test, and patient interviews., Methods: CSF leakage sites were identified using computed tomography myelography, radioisotope cisternography, and the overflow leak test in 14 patients with CSF hypovolemia. The patients were also asked about their history with regard to potential trauma. EBP was performed, and the accuracy of leakage site identification was assessed., Results: Conventional imaging identified a leakage site in 7 of 14 patients, and in most cases it was in the lumbar spine. In the remaining 7 cases, the overflow leak test and ascertaining a history of trauma facilitated identification of the cervical spine as a leakage site. The site of the EBP was the cervical spine in 10 patients and the lumbar spine in 4 patients. Complete recovery was observed in 13 of 14 patients., Conclusions: The cervical spine was a common leakage site in this study. Leakage in the cervical spine was undetectable via conventional imaging, suggesting that many cases of cervical spine leakage may remain undetected., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Glioma stem cells (GSCs) are responsible for tumor initiation, therapeutic resistance, and recurrence. CD146 is mainly expressed in dividing GSCs and regulates cell cycle progression. However, the evaluation of the efficacy of targeted therapy against CD146 in vivo remains to be investigated. In this study, the authors aimed to develop gene therapy targeting GSCs using chitosan oligosaccharide lactate (COL) nanoparticles (NPs) conjugated with folic acid-polyethylene glycol (FA-PEG-COL NPs) for in vitro and in vivo delivery of CD146 small-interfering RNA (siCD146) and to determine the effect of CD146 knockdown on tumor growth., Methods: To examine the uptake of NPs by tumor cells, immunofluorescence staining, flow cytometry, and in vivo imaging were performed. The knockdown effect of siCD146 was measured by western blot and water-soluble tetrazolium salt-8 assay in mouse glioma cells. The efficacy of siRNA therapy-targeted GSCs was evaluated by monitoring tumor growth through in vivo imaging and histological analysis., Results: In vivo accumulation of the FA-PEG-COL NPs in subcutaneous and intracranial gliomas following NP administration via a mouse tail vein was observed. Additionally, in vitro delivery of siCD146 ionically cross-linked NPs, reduced CD146 levels, and suppressed growth in the glioma tumor sphere. Evaluation of the in vivo therapeutic effects of siCD146-cross-linked NPs in a mouse glioma model revealed significant suppression of intracranial tumor growth, with complete removal of the tumor observed in some mice on histological examination. Furthermore, delivery of siCD146 significantly reduced the Ki-67 index in residual tumor tissues relative to that in control mice., Conclusions: CD146 is a potential therapeutic target, and folic acid-conjugated NPs delivering siRNA may facilitate gene therapy in malignant gliomas.

Background: 5-Aminolevulinic acid (5-ALA) is useful as a photodynamic agent, but its use commonly leads to hypotension. Although avoiding a mean arterial pressure (MAP) < 60 mmHg is important, the incidence of MAP < 60 mmHg when using 5-ALA is unclear. Therefore, we conducted a retrospective study to assess the incidence of post-induction hypotension and identified risk factors of this phenomenon., Methods: One-hundred and seventy-two consecutive patients who underwent transurethral resection of the bladder tumor or craniotomy with the use of 5-ALA were enrolled. The primary outcome was the incidence of post-induction hypotension, defined as MAP < 60 mmHg during the first 1 h after anesthesia induction. We divided participants into the normal blood pressure group (group N) and the hypotension group (group L)., Results: The incidence of post-induction hypotension was 70% (group L = 121, group N = 51). Multivariate analysis revealed that female sex was an independent factor of post-induction hypotension (odds ratio [OR] 3.95; 95% confidence interval [CI] 1.21-12.97; p = 0.02). Systolic blood pressure < 100 mmHg before anesthesia induction and general anesthesia were also identified as significant independent factors (OR 13.30; 95% CI 1.17-151.0; p = 0.04 and OR 25.84; 95% CI 9.80-68.49; p < 0.001, respectively)., Conclusions: The incidence of post-induction hypotension was 70% in patients using 5-ALA. Female sex, systolic blood pressure < 100 mmHg before anesthesia induction, and general anesthesia might be independent factors of post-induction hypotension when using 5-ALA.

A hybrid operating room(Hybrid OR), where operative equipment and flat panel angiography are both available, is becoming common for complex cerebrovascular surgery. However, the current Hybrid OR remains suboptimal as it is not cost-effective and contains uncomfortable operating beds, and a single-plane flat panel. Therefore, we introduced a novel Hybrid OR system, which has a biplane flat panel detector and three mutually exchangeable tailor-made operating beds. In this article, we report our preliminary experience of this novel Hybrid OR, focusing on improved cost-effectiveness by the availability of diagnostic angiography and standard endovascular surgery, optimal selection of three different types of operating beds, and procedural workflow in individual hybrid cerebrovascular surgery.

Background: Glial cells such as astrocytes and microglia play an important role in the central nervous system via communication between these glial cells. Activated microglia can exhibit either the inflammatory M1 phenotype or the anti-inflammatory M2 phenotype, which influences astrocytic neuroprotective functions, including engulfment of cell debris. Recently, extracellular zinc has been shown to promote the inflammatory M1 phenotype in microglia through intracellular zinc accumulation and reactive oxygen species (ROS) generation., Purpose: Here, we investigated whether the zinc-enhanced inflammatory M1 phenotype of microglia affects the astrocytic engulfing activity., Methods: Engulfing activity was assessed in astrocytes treated with microglial-conditioned medium (MCM) from lipopolysaccharide (LPS)-activated or from ZnCl 2 -pretreated LPS-activated M1 microglia. The effect of zinc on microglia phenotype was also validated using the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the ROS scavenger Trolox., Results: Although treatment of astrocytes with LPS showed no significant effect on the engulfing activity, MCM from LPS-induced M1 microglia increased the beads uptake by astrocytes. This increased uptake activity was suppressed when MCM from LPS-induced M1 microglia pretreated with ZnCl 2 was applied to astrocytes, which was further abolished by the intracellular zinc chelator TPEN and the ROS scavenger Trolox. In addition, expression of P2×7 receptors (P2×7R) was increased in astrocytes treated with MCM derived from M1 microglia but not in the M1 microglia pretreated with ZnCl 2 ., Conclusion: These findings suggest that zinc pre-treatment abolishes the ability of LPS-induced M1 microglia to increase the engulfing activity in astrocytes via alteration of astrocytic P2×7R., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Introduction: Astroblastoma is a rare, supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease., Case Presentation: A 6-year-old boy presented with headache and nausea. CT and MRI revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MRI 13 months after surgery suggested local recurrence, and an enlargement was found 3 months later. Stereotactic radiotherapy(SRT)was performed. MRI after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, 11 C-methionine positron emission tomography(PET)revealed radiation necrosis. The last follow-up MRI 15 months after SRT showed no further recurrence., Conclusion: Astroblastoma is rare, therefore, no optimal management is known. SRT may be effective to treat recurrent astroblastomas. 11 C-methionine PET/CT was useful to differentiate metastatic disease from radiation necrosis.

Objective: To identify a proximal anterior circulation occlusion for effectively administering immediate mechanical thrombectomy by developing a novel, simple diagnostic scale to predict the occlusion, to compare its validity with available scales, and to assess its utility., Methods: To develop a novel clinical scale, we retrospectively analyzed a cohort of 429 patients with acute ischemic stroke from a single center. The novel scale GAI 2 AA was applied to a prospective cohort of 259 patients from 3 stroke centers for external validation. The utility of the scale as an in-hospital triage was compared for the temporal factors of 158 patients with the occlusion., Results: In a scale-developmental phase, those with a proximal anterior circulation occlusion had significantly more frequent signs of hemispheric symptoms, including gaze palsy, aphasia, inattention, arm paresis, and atrial fibrillation. The GAI 2 AA scale was developed using consolidated hemispheric symptoms and was scored as follows: score = 2, arm paresis score = 1, and atrial fibrillation score = 1. A cutoff value ≥3 was optimal for the correlation between sensitivity (88%) and specificity (81%), with a C statistic of 0.90 (95% confidence interval 0.87-0.93). External validation indicated that discrimination was significantly better than or not different from that of available complex scales. Door-to-puncture time was significantly reduced (91 [82-111] vs 52 [32-75] minutes, p < 0.001)., Conclusion: The GAI 2 AA scale showed high sensitivity and specificity when an optimal cutoff score was used and was useful as an in-hospital triage tool., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

We have developed an acceptance-cone-tunable (ACT) electron spectrometer for the highly efficient constant-energy photoelectron mapping of functional materials. The ACT spectrometer consists of the hemispherical deflection analyzer with the mesh-type electrostatic lens near the sample. The photoelectron trajectory can be converged by applying a negative bias to the sample and grounding the mesh lens and the analyzer entrance. The performance of the present ACT spectrometer with neither rotating nor tilting of the sample is demonstrated by the wide-angle observation of the well-known π-band dispersion of a single crystalline graphite over the Brillouin zone. The acceptance cone of the spectrometer is expanded by a factor of 3.30 when the negative bias voltage is 10 times as high as the kinetic energy of photoelectrons.

Unruptured posterior communicating artery aneurysms with oculomotor nerve palsy are at high risk of rupture, and early intervention is recommended to prevent aneurysm bleeding and to improve oculomotor function. Both surgical clipping and endovascular coiling are available, and either of them is applied according to the anatomical condition and patient's comorbidity. In this article, we describe a case of an unruptured posterior communicating artery aneurysm with oculomotor nerve palsy, which was initially treated with surgical clipping. Owing to ventricular tachycardia during surgery, the craniotomy was discontinued and switched to endovascular coiling. In this operation, use of a hybrid operating room for coiling enabled adequate heparinization and immediate recraniotomy to prevent ischemic and hemorrhagic complications, respectively.

Background and Purpose: Return to work (RTW) after stroke is the ultimate goal of the working population to achieve economic independence and well-being. Previous studies have reported lower RTW rates of blue-collar workers versus white-collar workers. Thus, investigating predictive factors for RTW of blue-collar workers is meaningful to improve RTW after stroke. Here, we investigate the physical, cognitive, and social factors associated with the RTW of blue-collar workers after stroke., Methods: Poststroke rehabilitation data for 71 patients aged 15-64 years who had been active blue-collar workers at stroke onset were analyzed from a single-center observational cohort database. Baseline characteristics, social background factors, and quantitative assessments of the upper limb, lower limb, and cognitive functions at discharge were analyzed to identify any association with RTW. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value of continuous valuables with significant associations., Results: Functional upper limb represented by an increasing Simple Test for Evaluating hand Function (STEF) score was independently associated with RTW of blue-collar workers by multivariable logistic regression analysis (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.14; p = .017). Correlation with self-employment status was also significant compared to that with employee status (OR, 185; 95% CI, 1.05-32400; p = .048). The cutoff value of the 100-point scale STEF to discriminate between RTW and non-RTW was 82., Conclusions: Functional upper limb and self-employment status were independent predictors for the RTW of blue-collar workers after stroke., (Copyright © 2019 Elsevier Inc. All rights reserved.)